POS0523 FATIGUE TRAJECTORIES IN PATIENTS WITH EARLY RHEUMATOID ARTHRITIS: A LONGITUDINAL ANALYSIS OF DATA FROM THE CareRA TRIAL
Authors: M. Doumen, S. Pazmino, D. Bertrand, D. De Cock, J. Joly, R. Westhovens, P. Verschueren
Journal: Annals of the Rheumatic Diseases (2022)

Background Fatigue is a common and impactful symptom of rheumatoid arthritis (RA). Given its heterogeneity and unpredictable nature, studies on contributing factors of RA-related fatigue should include multidimensional measures of fatigue and assess these longitudinally with multivariate methods, starting early in the disease. Objectives We aimed to explore the longitudinal course of fatigue and its predictors among patients with early RA starting DMARD therapy. Methods Data came from the 2-year treat-to-target trial Care in early RA (CareRA) and its 3-year extension. Fatigue was measured based on visual analog scale (VAS), Multidimensional Fatigue Inventory (MFI), and Short-Form 36 (SF-36). Longitudinal fatigue trajectories were identified with multivariable growth mixture modeling. Baseline and early predictors of trajectory membership, including treatment response, were studied with multinomial logistic regression adjusted for age, gender, and treatment type. Patient global assessment (PGA), pain (VAS), and disability (HAQ) were studied in separate models because of collinearity (Spearman r &gt; 0.60). For all models, posterior probabilities of trajectory assignment were included in the regression as weights to account for classification uncertainty. Treatment response was defined, based on whether remission (DAS28-CRP &lt; 2.6) was achieved by week 16 and sustained until year 2, as either early persistent response, secondary failure, or delayed response. Results In total, 356 and 244 patients were included in the 2-year and 5-year analyses, respectively. Mean (SD) fatigue (VAS) at inclusion was 48/100 (24). Four fatigue trajectories were identified: Rapid, Gradual, and Transient Improvement, and Early Deterioration, consisting of 10%, 14%, 56%, and 20% of patients, respectively (Figure 1). Higher PGA, pain and HAQ at baseline were associated with increased probability of Rapid Improvement compared to Transient Improvement or Early Deterioration (Table 2). Secondary treatment failure and delayed treatment response strongly increased the probability of less positive fatigue trajectories when compared to early persistent response. Figure 1. Latent trajectories of fatigue evolution over the first 2 years in CareRA (n = 356). Conclusion The longitudinal course of fatigue in early RA is dynamic but highly refractory, with less than 25% of patients making lasting improvements and 20% even experiencing worsening fatigue despite intensive DMARD therapy. Remarkably, a higher perceived disease impact at baseline was associated with an increased probability of fatigue improvement, possibly reflecting the fluctuating nature of this complex symptom. However, early inflammatory disease control appears to be the most important contributor to improved long-term fatigue outcomes, illustrating the far-reaching impact of the therapeutic window of opportunity in early RA. References / Table 1. Predictors of fatigue trajectory membership Gradual improvement Transient improvement Early deterioration OR (95% CI) p OR (95% CI) p OR (95% CI) p Fatigue (0-100) 1.01 (0.99; 1.04) 0.32 0.99 (0.97; 1.01) 0.16 0.98 (0.96; 1.00) 0.07 PGA (0-100) 0.98 (0.95; 1.01) 0.11 0.96 (0.94; 0.99) 0.003 0.95 (0.92; 0.98) &lt;0.001 Tender joints (0-28) 1.00 (0.91; 1.13) 0.82 1.00 (0.91; 1.09) 0.97 0.99 (0.88; 1.11) 0.80 Swollen joints (0-28) 1.01 (0.90; 1.15) 0.82 0.99 (0.89; 1.10) 0.83 0.93 (0.81; 1.06) 0.30 CRP (mg/dL) 1.00 (0.98; 1.01) 0.67 0.99 (0.98; 1.01) 0.36 1.00 (0.97; 1.02) 0.66 Pain (0-100) 0.99 (0.96; 1.02) 0.36 0.96 (0.94; 0.98) 0.002 0.95 (0.92; 0.98) &lt;0.001 HAQ (0-3) 1.07 (0.52; 2.20) 0.85 0.55 (0.30; 1.01) 0.05 0.24 (0.11; 0.51) &lt;0.001 SF-36 Mental Component Score (0-100) 1.00 (0.96; 1.04) 0.97 1.02 (0.99; 1.06) 0.23 1.02 (0.98; 1.06) 0.34 Treatment response Secondary failure 2.22 (0.78; 6.32) 0.13 3.87 (1.57; 9.55) 0.003 7.88 (2.68; 23.13) &lt;0.001 Delayed response 2.93 (0.70; 12.15) 0.14 6.82 (1.91; 24.44) 0.003 11.14 (2.33; 53.19) 0.003 Disclosure of Interests Michaël Doumen: None declared, Sofia Pazmino: None declared, Delphine Bertrand: None declared, Diederik De Cock: None declared, Johan Joly: None declared, Rene Westhovens Speakers bureau: - Celltrion - Galapagos - Gilead, Consultant of: - Celltrion - Galapagos - Gilead, Patrick Verschueren Speakers bureau: - MSD - Eli Lilly - Galapagos, Consultant of: - Sanofi - Galapagos - Gilead - Pfizer, Grant/research support from: Pfizer Chair Management of Early Rheumatoid Arthritis at KU Leuven Belgium